Multishell Diffusion MR Tractography Yields Morphological and Microstructural Information of the Anterior Optic Pathway: A Proof-of-Concept Study in Patients with Leber’s Hereditary Optic Neuropathy

Abstract

Tractography based on multishell diffusion-weighted magnetic resonance imaging (DWI) can be used to estimate the course of myelinated white matter tracts and nerves, yielding valuable information regarding normal anatomy and variability. DWI is sensitive to the local tissue microstructure, so tractography can be used to estimate tissue properties within nerve tracts at a resolution of millimeters. This study aimed to test the applicability of the method using a disease with a well-established pattern of myelinated nerve involvement. Eight patients with LHON and 13 age-matched healthy controls underwent tractography of the anterior optic pathway. Diffusion parameters were compared between groups, and for the patient group correlated with clinical/ophthalmological parameters. Tractography established the course of the anterior optic pathway in both patients and controls. Localized changes in fractional anisotropy were observed, and related to estimates of different tissue compartments within the nerve and tract. The proportion of different compartments correlated with markers of disease severity. The method described allows both anatomical localization and tissue characterization in vivo, permitting both visualization of variation at the individual level and statistical inference at the group level. It provides a valuable adjunct to ex vivo anatomical and histological study of normal variation and disease processes.

Methods of diffusion MRI tractography for localization of the anterior optic pathway: A systematic review of validated methods

“…One study was excluded because it was conducted ex vivo on anatomical dissection ( Roebroeck et al, 2008 ). The remaining 39, published between 2007 and 2022, were included in the systematic review ( Akazawa et al, 2010 , Allen et al, 2018 , Altıntaş et al, 2017 , Ather et al, 2019 , Chakravarthi et al, 2021 , Davies-Thompson et al, 2013 , de Blank et al, 2013 , Ge et al, 2015 , Hajiabadi et al, 2015 , Hajiabadi et al, 2016 , He et al, 2021 , Ho et al, 2019 , Hodaie et al, 2010 , Hofer et al, 2010 , Jacquesson et al, 2019a , Jin et al, 2019 , Kamali et al, 2014 , Kammen et al, 2016 , Lacerda et al, 2021 , Lecler et al, 2018 , Liang et al, 2021 , Lin et al, 2018 , Lober et al, 2012 , Ma et al, 2016 , Maleki et al, 2012 , Manners et al, 2022 , Miller et al, 2019 , Puzniak et al, 2019 , Puzniak et al, 2021 , Salmela et al, 2009 , Staempfli et al, 2007 , Takemura et al, 2019 , Tao et al, 2009 , Techavipoo et al, 2009 , Wu et al, 2019 , Yang et al, 2011 , Yoshino et al, 2016 , Zhang et al, 2012b , Zolal et al, 2017 ) .

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“…Eight (20.5%) studies were conducted only on healthy volunteers ( Akazawa et al, 2010 , He et al, 2021 , Hofer et al, 2010 , Jin et al, 2019 , Kamali et al, 2014 , Kammen et al, 2016 , Maleki et al, 2012 , Staempfli et al, 2007 ), seven (17.9%) in patients affected by genetic conditions (e.g., albinism, congenital achiasma, Leber’s hereditary optic neuropathy) ( Ather et al, 2019 , Davies-Thompson et al, 2013 , Lecler et al, 2018 , Manners et al, 2022 , Puzniak et al, 2019 , Puzniak et al, 2021 , Takemura et al, 2019 ), three (7.7%) in patients affected by ophthalmological pathologies (e.g., amblyopia, aniridia, glaucoma) ( Allen et al, 2018 , Altıntaş et al, 2017 , Miller et al, 2019 ), nineteen (48.7%) in patients with tumors or other expansive processes ( de Blank et al, 2013 , Ge et al, 2015 , Hajiabadi et al, 2015 , Hajiabadi et al, 2016 , Ho et al, 2019 , Hodaie et al, 2010 , Jacquesson et al, 2019a , Liang et al, 2021 , Lin et al, 2018 , Lober et al, 2012 , Ma et al, 2016 , Salmela et al, 2009 , Tao et al, 2009 , Wu et al, 2019 , Yoshino et al, 2016 , Zhang et al, 2012b , Zolal et al, 2017 ), one (2.6%) in patients affected by demyelinating disorders (e.g., multiple sclerosis, neuromyelitis optica) ( Techavipoo et al, 2009 ), and two (5.1 %) in patients with other pathologies (traumas, epilepsy) ( Lacerda et al, 2021 , Yang et al, 2011 ) .…”

“…Twenty-eight studies (71.8%) performed tractography of the whole anterior optic pathway ( Akazawa et al, 2010 , Allen et al, 2018 , Altıntaş et al, 2017 , Ather et al, 2019 , Chakravarthi et al, 2021 , Davies-Thompson et al, 2013 , de Blank et al, 2013 , Ge et al, 2015 , He et al, 2021 , Ho et al, 2019 , Hodaie et al, 2010 , Hofer et al, 2010 , Jacquesson et al, 2019a , Kamali et al, 2014 , Lacerda et al, 2021 , Liang et al, 2021 , Lin et al, 2018 , Lober et al, 2012 , Ma et al, 2016 , Manners et al, 2022 , Puzniak et al, 2019 , Puzniak et al, 2021 , Salmela et al, 2009 , Staempfli et al, 2007 , Tao et al, 2009 , Yang et al, 2011 , Yoshino et al, 2016 , Zhang et al, 2012b ), three (7.6%) reconstructed only the optic nerves and chiasm ( Miller et al, 2019 , Techavipoo et al, 2009 , Zolal et al, 2017 ), two (5.1%) the optic nerves and tracts ( Lecler et al, 2018 , Wu et al, 2019 ), and the remaining six (15.4%) only the optic chiasm and tracts ( Hajiabadi et al, 2015 , Hajiabadi et al, 2016 , Jin et al, 2019 , Kammen et al, 2016 , Maleki et al, 2012 , Takemura et al, 2019 ).…”

“…Thirty-one studies (79.5%) were conducted using 3 T MRI ( Allen et al, 2018 , Altıntaş et al, 2017 , Ather et al, 2019 , Davies-Thompson et al, 2013 , de Blank et al, 2013 , Ge et al, 2015 , He et al, 2021 , Ho et al, 2019 , Hodaie et al, 2010 , Hofer et al, 2010 , Jacquesson et al, 2019a , Jin et al, 2019 , Kamali et al, 2014 , Kammen et al, 2016 , Liang et al, 2021 , Lin et al, 2018 , Lober et al, 2012 , Ma et al, 2016 , Maleki et al, 2012 , Manners et al, 2022 , Miller et al, 2019 , Puzniak et al, 2019 , Puzniak et al, 2021 , Salmela et al, 2009 , Staempfli et al, 2007 , Takemura et al, 2019 , Techavipoo et al, 2009 , Wu et al, 2019 , Yoshino et al, 2016 , Zolal et al, 2017 ), seven (17,5%) at 1.5 T ( Akazawa et al, 2010 , Hajiabadi et al, 2015 , Hajiabadi et al, 2016 , Lacerda et al, 2021 , Tao et al, 2009 , Yang et al, 2011 , Zhang et al, 2012b ) and one (2.5%) used both 3 T and 1.5 T scanners ( Chakravarthi et al, 2021 ). Repetition time (TR) and echo time (TE) ranged between 2300 and 17000 ms and 8.1–157 ms respectively.…”

Assessing robustness of quantitative susceptibility-based MRI radiomic features in patients with multiple sclerosis

“…DWI images were skull-stripped (Brain Extraction Tool 40 [BET]) from the Functional Magnetic Resonance Imaging of the Brain [FMRIB] Software Library 41 (FSL) and denoised (dwidenoise function of MRtrix3 42 ) using a principal component analysis approach; susceptibility-related distortion was estimated (topup function of FSL) and correction for susceptibility, eddy currents effects, and signal dropout was performed 43 (eddy_openmp function of FSL). FLAIR, DWI, and QSM images were linearly registered (FSL’s Linear Image Registration Tool 44 , 45 [FLIRT]) to the corresponding MPRAGE images.…”